The primary objective of this study is to assess the effects of standard pharmacologic treatments of the clinical depression on platelet activation PA). Increased PA is present in clinical depression, and has been implicated as one mechanism that may explain the link between depression and coronary heart disease (CHD) events. The investigators' preliminary work indicates that platelet secretion in increased in clinical depression, and that pharmacologic treatment with the selective serotonin reuptake inhibitor sertraline attenuates this increase. They also found evidence that depressed patients with a family history of CHD have increased PA. In the present application, the investigators seek to extend these findings by (a) performing a double-blind, placebo-controlled trial of sertraline and (b) assessing the effects of another pharmacologic treatment for depression (bupropion) on PA. As in previous studies, PA will be assessed by state-of-the-art flow cytometric detection, using methods developed and standardized in our laboratory. After initial PA testing, a total of 180 patients will be randomized to receive either sertraline or placebo for 8 weeks, with retesting at the end of this time period. A control group of 70 nondepressed individuals of similar age and gender composition will also be tested twice over 8 weeks. After follow-up measures for PA are taken, the blind will be broken and patients previously on placebo will be given 8 weeks of treatment with bupropion (an antidepressant medication that affects dopamine and norepinephrine pathways without affecting serotonin pathways). A final PA measure will be performed at the end of this 8-week treatment, in order to a) assess the stability of the response to sertraline and b) assess the open-label effects of bupropion. The investigators anticipate that 144 subjects will complete the entire protocol. The hypotheses for the study are: (1) PA is increased in depressed patients relative to controls, with the highest levels found among depressed patients with a family history of CHD; (2) Sertraline decreases PA in depressed patients relative to placebo; and (3) Bupropion, an antidepressant with nonserotonergic mechanisms of action, also decreases PA. This work will contribute to the understanding of mechanisms and treatment for depression so as to diminish CHD risk, particularly among those with a family history of CHD.